Cancer is a class of disease characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue of by implantation into distant sites via metastasis. Cancer affects people at all ages, but risk tends to increase with age. Cancer is a leading cause of death in developed countries. Adenocarcinoma is one form of cancer that originates in glandular tissues and/or has secretory properties. Adenocarcinomas can originate in many different tissues, such as the lung, breast, prostate, colon, stomach, pancreas, and cervix.
Lung cancer is the leading cause of cancer deaths in the United States, among both men and women. It is now the most common form of cancer diagnosed in the United States and a major cause of death. Lung cancer accounts for 14% of all cancers and 28% of all cancer deaths. The American Cancer Society estimates annual lung cancer deaths in the United States at about 163,510 in 2005 (Jemal et al., CA Cancer J. Clin. 55:10-30, 2005).
Lung cancers are divided into two general groups: small cell and non-small cell lung cancer. Small cell lung cancer spreads aggressively and accounts for about 20 percent of lung cancers in the United States. Non-small cell lung cancer accounts for the remaining 80 percent of lung cancers. There are three major categories of non-small cell lung cancer (NSCLC): (i) squamous cell carcinoma; (ii) adenocarcinoma; and (iii) large cell carcinoma. Adenocarcinoma is the predominant histological subtype of NSCLC (Devesa et al., Int. J. Cancer 117:294-9, 2005). Even when curative resection of early-stage NSCLC on a patient is performed, the risk of developing metastasis remains substantial. Lymph node metastasis and distant metastases through lymph and blood flow frequently occur and prove fatal; the 5-year survival rate of patients in pathological stage IA and IB are only 67% and 57%, respectively (Mountain, Cell 100:57-70, 2000).
Several mRNA and microRNA microarray-based studies have demonstrated that there can be unique molecular profiles of tumor tissues associated with metastasis and survival. However, a need remains for a set of markers that can be used to determine the prognosis of a subject, or that can be used to determine if NSCLC will metastasize.
Intensive research on prevention, causes, diagnosis and treatment of adenocarcinomas, such as lung cancer, is ongoing. In spite of this considerable research, patients' lung cancers are often in advanced stages at the time of detection, and current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients. Consequently, new methods to prevent, diagnose and treat lung cancer are needed.